The role of Mg²⁺ in immune cells

The physiological and clinical relevance of Mg²⁺ has evolved over the last decades. The molecular identification of multiple Mg²⁺ transporters (Acdp2, MagT1, Mrs2, Paracellin-1, SLC41A1, SLC41A2, TRPM6 and TRPM7) and their biophysical characterization in recent years has improved our understanding of Mg²⁺ homeostasis regulation and has provided a basis for investigating the role of Mg²⁺ in the immune system. Deletions and mutations of Mg²⁺ transporters produce severe phenotypes with more systemic symptoms than those seen with Ca²⁺ channel deletions, which tend to be more specific and less profound. Deficiency of the Mg²⁺ permeable ion channels TRPM6 or TRPM7 in mice is lethal at embryonic day 12.5 or at day 6.5, respectively, and, even more surprisingly, chicken DT40 B cells lacking TRPM7 die after 24–48 h. Recent progress made in Mg²⁺ research has helped to define underlying mechanisms of two hereditary diseases, human Hypomagnesemia (TRPM6 deletion) and X-chromosomal immunodeficiency (MagT1 deletion), and has revealed a potential new role for Mg²⁺ as a second messenger. Future elucidation of human Mg²⁺ transporters (Mrs2, SLC41A1, SLC41A2, TRPM7) expressed in immunocytes, beyond MagT1 and TRPM6, will widen our knowledge about the potential role of Mg²⁺ in the activation of the immune response.